Differences in basal and stimulated cyclic AMP content in calvaria bones from normal mice and mice with an impaired lysosomal function (beige mice)

Earlier we have shown that bone resorption is impaired in cultured calvaria from beige mice (an animal equivalent of the Chediak-Higashi syndrome in man). In the present study we have compared the concentrations of cyclic AMP and cyclic GMP in calvarial bones from beige mice with the nucleotide concentrations in bones from corresponding normal mice. In six independent experiments the basal concentrations of cyclic AMP was significantly (P less than 0.01) higher in bones from beige mice (on an average 50% augmented). The ratio of cyclic AMP/cyclic GMP was 2.43 times higher (P less than 0.01) in bones from beige mice. After stimulation with the phosphodiesterase inhibitor isobutylmethylxanthine and prostaglandin E2 no significant differences of cyclic AMP concentrations between beige and control mice could be registered. The response to adenosine was significantly higher (P less than 0.005) in bones from beige mice (4.3 +/- 0.4-fold of basal cyclic AMP concentrations, mean +/- SE) compared to control mice (1.9 +/- 0.4-fold of basal, mean +/- SE). The increased basal concentration of cyclic AMP in calvaria from beige mice may be due to increased sensitivity to some agonists, such as adenosine, rather than simply being a function of cell mass.     

The effect of changes in alcohol consumption on mortality and admissions with alcohol-related diagnoses in Stockholm County-a time series analysis

Aim. To study the effect of changes in per capita alcohol sales and indicators of alcoholism treatment on admissions to inpatient care and mortality for liver cirrhosis and alcoholism, alcohol intoxication and alcohol psychosis (AAA). Design. Bivariate and multivariate time series analyses was conducted by applying the ARIMA-modelling technique. Setting and participants. from Stockholm County 1980-94 with a population of 1.7 million people. Measurements. of alcohol and disulfiram/calcium carbimide were used as input variables. Inpatient data (from the Stockholm Inpatient Care Register) and mortality data (from the Cause of Death Register) on all cases with alcoholism, alcohol psychosis and alcohol intoxication (AAA) and liver cirrhosis as underlying or contributory diagnoses were used as output variables. Findings. Alcohol sales affected the cirrhosis rate. For cirrhosis mortality, but not for cirrhosis admissions, the effect was not only direct but also distributed over time. Significant direct and time lag effects of alcohol sales on both AAA series and cirrhosis admissions were found only during earlier, shorter periods, e.g. 1980-90. All four output series showed significant effects of sales of disulfiram/calcium carbimide and were the only significant predictors for the two AAA endpoints for the whole study period. Conclusions. These results suggest that to reduce the rate of alcohol-related problems caused by socially deteriorated and severely alcohol-dependent subjects (i.e. AAA), reduction of overall consumption should be complemented by treatment of alcohol-dependent subjects. All analyses were conducted on quarterly data Data on sales     

AMINO ACID INCORPORATION INTO BRAIN SUBCELLULAR FRACTIONS IN EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS

The in vitro protein synthetic capactiy of brain slices from guinea-pigs in the late stage (17-18 days post-induction) of experimental allergic encephalomyelitis was increased over that of Freund's adjuvant injected controls, as determined by the rate of (14C)-leucine incorporation into both tris-soluble and tris-insoluble proteins. All subcellular fractions prepared from incubated slices showed increased incorporation, with a crude nuclear fraction having the largest increase. Isolated brain mitochondria from EAE animals incorporated more amino acid into protein during the late stage of the disease, while isolated microsomes and "pH5 enzymes" show decreased amino acid incorporation compared with controls in the late stage of EAE. Polyacrylamide gel electrophoresis of acidic, soluble proteins isolated from (3H)-leucine labeled nuclear or synaptosomal fractions revealed that increases of incorporation were generalized, and not restricted to a few proteins.     

Circulatory Effects of Haemorrhage during Sodium Nitroprusside Induced Hypotension A Study in the Rat

The haemodynamic changes induced by acute moderate blood loss were investigated in rats during normotensive halothane anaesthesia and during sodium-nitroprusside-induced hypotensive anaesthesia, respectively. Following haemorrhage in the normotensive group, mean arterial blood pressure, heart rate and left cardiac work decreased. Cardiac output was reduced non-significantly. Blood flow was redistributed to favour cerebral, coronary, renal and hepatic circulation, mainly at the expense of blood flow to the carcass. Following haemorrhage in the hypotensive group, cardiac output increased significantly. Mean arterial pressure, heart rate and left cardiac work were unchanged. Absolute values for cerebral, coronary, renal and hepatic blood flow were maintained or even increased, while blood flow to the carcass was unchanged.     

Total Body Bone Mineral in Light-for-Gestational-Age Infants and Appropriate-for-Gestational-Age Infants

ABSTRACT. Dual-photon-absorptiometry using ¹⁵³Gd in a whole body scanner was used to measure total body bone mineral in 51 newborn infants. In preterm light-for-gestational-age infants total body bone mineral was 12.6 g v.s. 25.6 g in preterm appropriate-for-gestational-age infants ( p < 0.05). In term light-for-gestational-age infants total body bone mineral was 41.4 g v. 84.2 g in term appropriate-for-gestational-age infants ( p < 0.00T). The correlations between gestational age and total body bone mineral was best described by exponential regression lines.     

A Randomized Study of Secondary Prevention of Early Stage Problem Drinkers in Primary Health Care

The subjects were recruited from participants in a health examination of random samples of the adult population in Stockholm county. Those aged 18–64years who admitted a high alcohol consumption (>40 g 100% ethanol/day) among men and <30 g among women) or had an elevated value of serum-gammaglutamyltransferase (GOT) (cut-off point 1.0 microkatal/l for men and 0.6 microkatal/l for women) or had certain other indications of a high alcohol consumption were included. More severe cases, and those with an elevated GOT due to reasons other than alcohol, were excluded. The remaining subjects, 70 men and 13 women, were allocated at random to either an intervention or a comparison group. An elevated GGT was the main inclusion criteria. The subjects in the comparison group were advised by the general practitioner to cut their alcohol consumption, while those in the intervention group made further visits to their general practitioner, who gave general support and used an elevated GGT as an indication of the recent level of alcohol consumption at consecutive visits. There were three visits on average, so we are comparing a group receiving advice with a group receiving further minimal intervention. At the one-year follow-up there were greater, however not significant, reductions in GGT-level, in self-reported alcohol consumption and in a ‘problem index’ in the minimal intervention group than in the comparison group.     

Release of nitric oxide during the experimental infection with Trypanosoma cruzi

We analysed the production of nitric oxide (NO) intermediates by cells from BALB/c mice infected with either virulent (Tulahuén or RA) or avirulent (CA-1) strains of Trypanosoma cruzi. Peritoneal or spleen cells from mice infected with T. cruzi released NO when incubated without further stimuli. Cells from mice during the acute stage of infection accumulated higher levels of inducible NO synthase mRNA and produced both, before and after lypopolysaccharide stimulation, higher amounts of NO than cells from mice chronically infected with T. cruzi. NO synthesis showed similar kinetics in connection with all three strains ofT. cruzi, but cells from mice inbred with the Tulahuén or RA strains released higher levels of IFN-γ, an activator of the NO pathways, than cells from mice infected with the CA-1 strain. In vivo administration of L-Ng-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of NO synthase, increased the susceptibility of mice to T. cruzi. We conclude that infection with T. cruzi induces NO production, and suggest that NO plays a role in the resistance against the parasite.